Myosin-II mediated traction forces evoke localized Piezo1-dependent Ca 2+ flickers

Piezo channels transduce mechanical stimuli into electrical and chemical signals to powerfully influence development, tissue homeostasis, and regeneration. Studies on Piezo1have largely focused on transduction of “outside-in” mechanical forces, and its response to internal, cell- generated forcesremains poorly understood. Here, using measurements of endogenous Piezo1activity and traction forces in native cellular conditions, we show that cellular traction forces generate spatially-restricted Piezo1-mediated Ca2+ flickersin the absence of externally- applied mechanicalforces. Although Piezo1channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flickeractivity is enriched near force-producing adhesions. The mechanical force that activates Piezo1arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1Ca2+ flickersallow spatial segregation of mechanotransductionevents, and that mobility allows Piezo1channels to explore a large number of mechanical microdomains and thus respond to a greater diversity of mechanical cues.